WO2022075764A1 - Composition visant à favoriser l'excrétion d'acide urique, comprenant un extrait complexe à base de plantes comme principe actif - Google Patents
Composition visant à favoriser l'excrétion d'acide urique, comprenant un extrait complexe à base de plantes comme principe actif Download PDFInfo
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- WO2022075764A1 WO2022075764A1 PCT/KR2021/013767 KR2021013767W WO2022075764A1 WO 2022075764 A1 WO2022075764 A1 WO 2022075764A1 KR 2021013767 W KR2021013767 W KR 2021013767W WO 2022075764 A1 WO2022075764 A1 WO 2022075764A1
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- WIPO (PCT)
- Prior art keywords
- uric acid
- hyperuricemia
- complex extract
- acid excretion
- excretion
- Prior art date
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Definitions
- the present invention relates to a composition for promoting uric acid excretion comprising a herbal complex extract as an active ingredient.
- Uric acid is a waste product generated by the decomposition of purines, and is mostly excreted in urine and feces in normal people.
- Hyperuricemia is defined as blood uric acid levels exceeding 6.8 to 7.0 mg/dL in men or 6 mg/dL in women. Hyperuricemia and gout are prevalent in China, Japan, Polynesia, and urban sub-Saharan Africa. . Hyperuricemia-related metabolic disorders include gout, as well as uric acid crystals, deposition of urate crystals in the joints, pain attacks of acute, monoarticular, inflammatory arthritis due to deposition of urate crystals in the renal tract, urolithiasis, nephrolithiasis and gout. include nephropathy. Long-term nephrolithiasis and gouty nephropathy are known to increase the risk of kidney damage and renal failure.
- gout is caused by an increase in the concentration of uric acid (a product that remains after the body metabolizes a substance called purine ingested through food) in the blood. It is a disease in which crystals are deposited in the cartilage, tendons, and surrounding tissues of the joint. This phenomenon causes joint inflammation and recurrent seizures accompanied by excruciating pain, and as gout nodules are deposited by urate crystals, joint deformation and disability occur. In addition to joint abnormalities, it causes various kidney diseases, and nephrolithiaisis (nephrolithiasis), which causes stones in the kidneys due to uric acid, may also appear.
- gout appears through stages such as asymptomatic hyperuricemia, acute gouty arthritis, intermittent gout, and chronic nodular gout.
- asymptomatic hyperuricemia the serum uric acid concentration is increased, but symptoms such as arthritis symptoms, gouty nodules, and uric acid nephropathy have not yet appeared.
- Acute gouty arthritis is a stage in which gout attacks or kidney stones occur after hyperuricemia lasting for at least 20 years, and the most characteristic symptom is an acute attack of very painful arthritis, which initially involves one joint Although there are no systemic symptoms, it gradually invades several joints and is accompanied by fever.
- Intermittent gout refers to the symptom-free period between gout attacks, with most experiencing a second attack between 6 months and 2 years after the first attack, and depending on the treatment, it increases in frequency, invading the joint.
- Chronic nodular gout looks similar to other types of arthritis when it goes through an intermittent period without gout and then into chronic nodular gout. Progressive stiffness and persistent pain occur in the affected joint.
- gout is known as a disease that can be successfully treated with a clear treatment, it is often accompanied by other diseases such as high blood pressure and chronic kidney failure.
- Patient effort is essential for a good prognosis for long-term treatment.
- Gout and hyperuricemia show clinical features such as hypertension, hyperlipidemia, increased blood sugar, and abdominal obesity, and do not meet the diagnostic criteria for metabolic syndrome, a complex disease that increases the risk of adult diseases such as atherosclerotic heart disease and type 2 diabetes. Metabolic syndrome is thought to have a close relationship. In Korea, it was reported that 44% of gout patients were accompanied by metabolic syndrome. Gout usually appears in the form of acute monoarthritis, but it can also involve a few joints or, rarely, polyarthritis.
- Non-steroidal anti-inflammatory drugs used in the treatment of acute gout are well known to inhibit the inflammatory response, and colchicine (colchicine), which exhibits anti-inflammatory action by inhibiting the activity and migration of white blood cells ), steroids are all drugs that can effectively treat gout attacks, and selective cyclooxygenase (COX-2) inhibitors are also known to have the same effect as existing nonsteroidal anti-inflammatory drugs.
- NSAIDs non-steroidal anti-inflammatory drugs
- colchicine colchicine
- COX-2 selective cyclooxygenase
- uric acid lowering agents are divided into xanthine oxidase (XO) inhibitors and uricosuric agents according to the mechanism.
- XO xanthine oxidase
- Febuxostat is also a xanthine oxidase inhibitor, but unlike allopurinol, it is a non-purine selective blocker and is mainly metabolized in the liver to form glucuronide. Most gout progresses chronically, and even if there are no symptoms, prophylactic anti-inflammatory drugs and lowering of uric acid concentration are used. Such preventive treatment should be used after the disease has been maintained for a period of time in a sedated state, otherwise the gout will recur more severely.
- maekmundong refers to the root of an orchid-like ornamental plant, which is harvested in spring and autumn, peeled, and then dried in the sun.
- the taste is sweet and slightly bitter, and in oriental medicine, it is used for heat stroke, heat stroke, myocarditis, chronic bronchitis, and emphysema.
- Omija is the fruit of the Schisandra tree, about 1cm in diameter, and has a deep red color. It is called omija because it can taste sweet, sour, bitter, salty and spicy. As it contains ingredients such as sijandrine, gomisin, citral, malic acid and citric acid, it is used as a tonic because it strengthens the heart, lowers blood pressure, and boosts immunity. It strengthens lung function and has antitussive and expectorant action, so it is helpful in treating cough and thirst.
- ginseng is used for body weakness, malaise, fatigue, loss of appetite, vomiting, diarrhea, helps the lungs function, produces a sap, and acts as an ophthalmologist.
- the pharmacological action has been reported to include cortical excitability and inhibition, balance, anti-fatigue, anti-aging, immune enhancement, cardiac contraction, gonadotrophin, hyperglycemia suppression, protein synthesis promotion, homeostasis maintenance, anticancer and detoxification action.
- Korean Patent No. 1715520 discloses a pharmaceutical composition for treating gout
- Korean Patent No. 1661793 discloses a hyperlipidemia improving agent, an anemia improving composition, uric acid level lowering composition, and food and drink. So far, there has been no disclosure of a composition for promoting uric acid excretion comprising the herbal complex extract of the present invention as an active ingredient.
- the present invention has been derived from the above needs, and the present invention provides a composition for promoting uric acid excretion comprising a herbal complex extract as an active ingredient, wherein the herbal complex extract reduces the amount of uric acid in the blood, and In addition to increasing the amount of acid, it has the effect of increasing the excretion rate of uric acid fraction, has the effect of reducing the expression of uric acid reuptake-related transporters URAT1 and GLUT9 in the kidney, which is the main organ for excretion of uric acid, and has the effect of inhibiting uric acid reuptake by URAT1 By confirming that there is, the present invention was completed.
- the present invention provides a health functional food composition for promoting uric acid discharge comprising a herbal complex extract consisting of maekmundong, omija and ginseng as an active ingredient.
- the present invention provides a pharmaceutical composition for preventing or treating hyperuricemia or hyperuricemia-related metabolic disorders caused by lowering uric acid excretion, comprising a herbal complex extract consisting of maekmundong, omija and ginseng as an active ingredient.
- the present invention relates to a composition for promoting uric acid excretion comprising a herbal complex extract as an active ingredient, wherein the herbal complex extract not only reduces the amount of uric acid in the blood and increases the amount of uric acid in the urine, but also increases the excretion rate of the uric acid fraction. It has the effect of reducing the expression of uric acid reuptake-related transporters URAT1 and GLUT9 in the kidney, which is a major organ for uric acid excretion, and has the effect of inhibiting uric acid reuptake by URAT1.
- N is a normal group
- PO is a control group administered with 150 mg/kg of potassium oxonate
- Allo is a positive control group administered with 10 mg/kg of allopurinol.
- ### indicates that the amount of uric acid in the serum of the control group increased statistically significantly compared to the normal group, p ⁇ 0.001, and *, **, *** indicate that the amount of uric acid in the serum of the extract or allopurinol administration group compared to the control group (PO) was statistically significant.
- * is p ⁇ 0.05
- ** is p ⁇ 0.01
- *** is p ⁇ 0.001.
- $ indicates that the herbal complex extract of the present invention significantly decreased the amount of uric acid in the serum compared to each single extract, and p ⁇ 0.05.
- N is a normal group
- PO is a control group
- Allo is a positive control group
- #, ##, ### indicate that the amount of uric acid or creatine in the serum of the control group increased or the amount of uric acid in the urine decreased statistically significantly, compared to the normal group, where # is p ⁇ 0.05, ## is p ⁇ 0.01, and ### is p ⁇ 0.001.
- Figure 3 is the result of confirming the expression effect of the major selective uric acid receptor 1 (URAT1) and glucose transporter 9 (GLUT9) that regulates uric acid reuptake in the kidney tissue in an animal model
- N is a normal group
- PO is potassium oxonate
- Allo which were administered to induce hyperuricemia, were allopurinol-administered groups as a positive control group.
- * indicates that the expression level of the uric acid reuptake receptor protein was decreased in the group administered with the herbal complex extract of the present invention compared to the control group, p ⁇ 0.05.
- the present invention relates to a health functional food composition for promoting uric acid excretion comprising a herbal complex extract consisting of maekmundong, omija and ginseng as an active ingredient.
- the herbal complex extract consisting of maekmundong, omija and ginseng may be prepared by a method comprising the following steps, but is not limited thereto:
- step 3 Concentrating the filtered extract of step 2) under reduced pressure and drying to prepare an extract.
- the extraction solvent is preferably water, a C 1 to C 4 lower alcohol or a mixture thereof, and more preferably an ethanol extract, but is not limited thereto.
- the extraction method of the herbal complex extract may use all conventional methods known in the art, such as filtration, hot water extraction, immersion extraction, reflux cooling extraction, and ultrasonic extraction. It is preferable to use a vacuum vacuum concentrator or a vacuum rotary evaporator for the concentration under reduced pressure in step 3), but is not limited thereto. In addition, drying under reduced pressure, vacuum drying, boiling drying, spray drying or freeze drying is preferable, but is not limited thereto.
- the health functional food composition may be prepared in any one formulation selected from powder, granule, pill, tablet, capsule, candy, syrup and beverage, or may be prepared by adding it to other foods or ingredients of foods, and according to a conventional method It can be suitably prepared.
- Examples of foods to which the active ingredient of the present invention can be added include meat, sausage, bread, chocolate, candy, snacks, confectionery, pizza, ramen, other noodles, gum, dairy products including ice cream, various soups, beverages, It may be in any one form selected from tea, drinks, alcoholic beverages and vitamin complexes, and includes all health functional foods in a conventional sense.
- the health functional food includes various nutrients, vitamins, minerals (electrolytes), synthetic and natural flavors, colorants and enhancers (cheese, chocolate, etc.), pectic acid and its salts, alginic acid and its salts, organic acids, protective colloidal thickeners, It may contain a pH adjuster, a stabilizer, a preservative, glycerin, alcohol, a carbonation agent used in carbonated beverages, and the like. In addition, it may contain the pulp for the production of natural fruit juices and vegetable beverages. These components may be used independently or in combination.
- the health functional food composition of the present invention may contain various flavoring agents or natural carbohydrates as additional ingredients.
- the natural carbohydrates include monosaccharides such as glucose and fructose, disaccharides such as maltose and sucrose, polysaccharides such as dextrin and cyclodextrin, and sugar alcohols such as xylitol, sorbitol, and erythritol.
- natural sweeteners such as taumartin and stevia extract, synthetic sweeteners such as saccharin and aspartame, and the like can be used.
- the herbal complex extract is preferably extracted by mixing maekmundong, Schisandra and ginseng in a weight ratio of 1 to 10:1 to 10:1 to 10, more preferably from 1 to 2:1 to 2:1 to 2 by weight. It is to be extracted by mixing, and most preferably, mixing in a weight ratio of 2:1:1, but not limited thereto.
- the present invention relates to a pharmaceutical composition for the prevention or treatment of hyperuricemia or hyperuricemia-related metabolic disorders caused by lowering of uric acid excretion comprising a herbal complex extract consisting of maekmundong, omija and ginseng as an active ingredient.
- the hyperuricemia-related metabolic disorder is preferably any one selected from acute or chronic gout, gouty flare, gouty arthritis, gouty nephrolithiasis, and gouty nephropathy, but is not limited thereto.
- the gouty flare refers to a symptom of redness due to inflammation or the like caused by gout.
- the active ingredient may further include a pharmaceutically acceptable carrier, excipient or diluent.
- the pharmaceutical composition of the present invention may be in various oral or parenteral formulations.
- formulation it is prepared using commonly used diluents or excipients such as fillers, extenders, binders, wetting agents, disintegrants, and surfactants.
- Solid preparations for oral administration include tablets, pills, powders, granules, capsules, etc., and these solid preparations include at least one excipient in one or more compounds, for example, starch, calcium carbonate, sucrose or lactose ( lactose), gelatin, etc.
- lubricants such as magnesium stearate and talc are also used.
- Liquid formulations for oral administration include suspensions, solutions, emulsions, syrups, etc.
- Formulations for parenteral administration include sterile aqueous solutions, non-aqueous solutions, suspensions, emulsions, lyophilized formulations, and suppositories.
- non-aqueous solvent and the suspending solvent propylene glycol, polyethylene glycol, vegetable oils such as olive oil, and injectable esters such as ethyl oleate may be used.
- base of the suppository witepsol, macrogol, tween 61, cacao butter, laurin paper, glycerol, gelatin, etc. can be used.
- composition of the present invention may be administered orally or parenterally, and when administered parenterally, it is preferable to select an external skin or intraperitoneal, rectal, intravenous, intramuscular, subcutaneous, intrauterine dural or intracerebrovascular injection method, most preferably It is used externally on the skin.
- composition according to the present invention is administered in a pharmaceutically effective amount.
- pharmaceutically effective amount means an amount sufficient to treat a disease at a reasonable benefit/risk ratio applicable to medical treatment, and the effective dose level is the type, severity, and drug activity of the patient. , can be determined according to factors including sensitivity to drug, administration time, administration route and excretion rate, duration of treatment, concurrent drugs, and other factors well known in the medical field.
- the composition of the present invention may be administered as an individual therapeutic agent or in combination with other therapeutic agents, may be administered sequentially or simultaneously with conventional therapeutic agents, and may be administered singly or multiple times. In consideration of all of the above factors, it is important to administer an amount that can obtain the maximum effect with a minimum amount without side effects, which can be easily determined by those skilled in the art.
- the dosage of the composition of the present invention can be used in various ranges depending on the weight, age, sex, health status, diet, administration time, administration method, excretion rate and severity of the disease of the patient.
- Example 1 Preparation of herbal complex extract consisting of maekmundong, omija and ginseng
- Maekmundong root (tuber) (LP, tuber of Liriope platyphylla )
- Schisandra fruit (SC, fruit of Schisandra chinensis )
- ginseng root (PG, root of Panax ginseng Meyer ) were mixed in a weight ratio of 2:1:1, and the 30% (v/v) ethanol was added as an extraction solvent so as to be 10 times the weight ratio of the crude drug complex, extracted under reflux for 3 hours, and then concentrated and dried.
- a hyperuricemia-inducing animal model In order to induce hyperuricemia in SD-rat, a hyperuricemia-inducing animal model, it was dissolved in 0.5% sodium carboxymethylcellulose (CMC-Na, pH 5.0) solution containing 0.1M sodium acetate. 150 mg/kg of potassium oxonate was intraperitoneally injected. Then, after 1 hour, 400 mg/kg of herbal complex extract, Maekmundong extract, Schisandra extract, and ginseng extract and 10 mg/kg of allopurinol as a positive control were mixed with 0.1% polyoxyethylene sorbitane monooleate in 0.01 M was suspended in PBS (phosphate buffered saline) buffer and administered orally. After 2 hours, blood was collected and the amount of uric acid in the blood was measured.
- CMC-Na, pH 5.0 sodium carboxymethylcellulose
- PBS phosphate buffered saline
- the amount of uric acid in the serum of the potassium oxonate-administered group was significantly increased, and in the group administered orally, the herbal complex extract of the present invention was statistically significantly decreased.
- the amount of uric acid in the serum of the herbal complex extract of the present invention was further reduced compared to the maekmundong, omija or ginseng extract alone constituting the herbal complex extract.
- a hyperuricemia-inducing animal model In order to induce hyperuricemia in SD-rat, a hyperuricemia-inducing animal model, it was dissolved in 0.5% sodium carboxymethylcellulose (CMC-Na, pH 5.0) solution containing 0.1M sodium acetate. 150 mg/kg of potassium oxonate was intraperitoneally injected. Then, after 1 hour, 100, 200, and 400 mg/kg of crude drug complex extract and 10 mg/kg of allopurinol as a positive control were mixed with 0.01M of PBS (phosphate) containing 0.1% of polyoxyethylene sorbitane monooleate (polyoxyethylene sorbitane monooleate). Buffered saline) was suspended in a buffer solution and administered orally for 5 days.
- CMC-Na, pH 5.0 sodium carboxymethylcellulose
- PBS phosphate
- polyoxyethylene sorbitane monooleate polyoxyethylene sorbitane monooleate
- uric acid assay kit (ab65344, abcam, USA).
- BUN blood urea nitrogen
- Example 3 after blood and urine were collected, kidney tissue was extracted, and the kidney tissue sample was urate/anion exchanger 1 (URAT1; extensor), a transporter involved in uric acid reabsorption using Pro-Prep protein extraction solution.
- URAT1 urate/anion exchanger 1
- GLUT9 glucose transporter 9
- the plasmid into which the URAT1 gene was inserted was linearized with a restriction enzyme, and cRNA was prepared using this as a template. After microinjection of the prepared cRNA into egg cells collected from northern frogs ( X. laevis), the cells were cultured for 26 to 48 hours so that the transport protein was expressed.
- an ND96 solution (96mM NaCl, 2mM KCl, 1.8mM CaCl 2 , 1mM MgCl 2 , 5mM HEPES, pH 7.4) containing 1 mM pyrazinecarboxylic acid was added to each well. treated and pre-incubated for 1 hour at room temperature.
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Abstract
La présente invention concerne une composition visant à favoriser l'excrétion d'acide urique, comprenant un extrait complexe à base de plantes comme principe actif. Non seulement l'extrait complexe à base de plantes réduit les taux d'acide urique dans le sang et augmente les taux d'acide urique dans les urines, mais il a également pour effet d'augmenter l'excrétion fractionnelle de l'acide urique, de réduire l'expression de l'URAT1 et du GLUT9, qui sont des transporteurs associés à la réabsorption de l'acide urique, dans le rein qui est un organe majeur pour l'excrétion d'acide urique, et d'inhiber la réabsorption de l'acide urique médiée par l'URAT1, et peut ainsi être utilisé efficacement comme aliment fonctionnel de santé pour favoriser l'excrétion d'acide urique, ou comme médicament pour le traitement de l'hyperuricémie provoquée par une excrétion d'acide urique réduite.
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JP2006016340A (ja) * | 2004-07-02 | 2006-01-19 | Kikkoman Corp | ザクロ抽出物を有効成分とする、血中尿酸値低下剤 |
CN110433226A (zh) * | 2019-08-13 | 2019-11-12 | 江阴持一堂医药科技有限公司 | 一种用于治疗痛风性关节炎或高尿酸血症的中药组合物和制剂及其制备方法和应用 |
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JP2006016340A (ja) * | 2004-07-02 | 2006-01-19 | Kikkoman Corp | ザクロ抽出物を有効成分とする、血中尿酸値低下剤 |
CN110433226A (zh) * | 2019-08-13 | 2019-11-12 | 江阴持一堂医药科技有限公司 | 一种用于治疗痛风性关节炎或高尿酸血症的中药组合物和制剂及其制备方法和应用 |
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